A Study to Evaluate the Efficacy and Safety of Infigratinib in Children and Adolescents With Achondroplasia (PROPEL3)

A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Infigratinib in Children 3 to <18 Years of Age With Achondroplasia: PROPEL 3

This is a Phase 3, multicenter, double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of infigratinib in children and adolescents with achondroplasia (ACH) who have completed at least 26 weeks of participation in the QED-sponsored study PROPEL (QBGJ398-001).

Study Overview

• Status: Enrolling by invitation
• Conditions: Achondroplasia
• Intervention / Treatment: Drug: Infigratinib 0.25 mg/kg/day; Drug: Placebo Comparator 0.25 mg/kg/day

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Capital Federal
    • Buenos Aires, Capital Federal, Argentina, C1245AAM
      • QED Investigative Site
• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • QED Investigative Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1C9
      • QED Investigative Site
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L1
      • QED Investigative Site
  • Quebec
    • Montréal, Quebec, Canada, H3C 3J7
      • QED Investigative Site
• France
  • Bron, France, 69677
    • QED Investigative Site
  • Paris, France, 75015
    • QED Investigative Site
  • Toulouse, France, 31059
    • QED Investigative Site
• Germany
  • Sachsen-Anhalt
    • Magdeburg, Sachsen-Anhalt, Germany, 39120
      • QED Investigative Site
• Italy
  • Milano, Italy, 20122
    • QED Investigative Site
  • Rome, Italy, 00168
    • QED Investigative Site
• Norway
  • Bergen, Norway, 5021
    • QED Investigative Site
  • Oslo, Norway, 0372
    • QED Investigative Site
• Singapore
  • Singapore, Singapore, 229899
    • QED Investigative Site
• Spain
  • Madrid, Spain, 28046
    • QED Investigative Site
  • Málaga, Spain, 29010
    • QED Investigative Site
  • Vitoria-Gasteiz, Spain, 01008
    • QED Investigative Site
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • QED Investigative Site
  • Bristol, United Kingdom, BS2 8AE
    • QED Investigative Site
  • Glasgow, United Kingdom, G12 0XH
    • QED Investigative Site
  • London, United Kingdom, SE1 7EH
    • QED Investigative Site
  • Manchester, United Kingdom, M13 9WL
    • QED Investigative Site
  • Sheffield, United Kingdom, S10 2TH
    • QED Investigative Site
• United States
  • California
    • San Francisco, California, United States, 94110
      • QED Investigative Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • QED Investigative Site
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • QED Investigative Site
  • Missouri
    • Columbia, Missouri, United States, 65203
      • QED Investigative Site
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • QED Investigative Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • QED Investigative Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • QED Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Inclusion Criteria:

  1. Subject must be 3 to <18 years of age at screening with growth potential defined as annualized height velocity of >1.5 cm/year over a period of at least 6 months, pubertal Tanner stage ≤4, and bone age ≤13 years in females and ≤15 years in males.

     Type of Subject and Disease Characteristics

  2. Subjects who have a diagnosis of ACH that has been documented clinically and confirmed by genetic testing.
  3. Subjects must have completed at least 26 weeks in the PROPEL (QBGJ398-001) study before study entry.
  4. Subjects are able to swallow oral medication.
  5. Subjects and parent(s), legal guardian(s), or caregivers are willing and able to comply with study visits and study procedures.
  6. Subjects are ambulatory and able to stand without assistance. Sex and Contraceptive/Barrier Requirements
  7. Negative pregnancy test in girls ≥10 years of age or girls of any age who have experienced menarche.

  8. If sexually active, subjects must be willing to use a highly effective method of contraception while taking study drug and for 3 months after the last dose of study drug.

     Informed Consent

  9. Signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol, must be obtained for each subject from their parent(s) or legal guardian and signed informed consent/assent must be obtained from the subject (when applicable)

Exclusion Criteria:

• Exclusion Criteria Medical Conditions

  1. Subjects who have hypochondroplasia or short stature condition other than ACH.
  2. Significant concurrent disease or condition that, in the view of the investigator and/or sponsor, would confound assessment of efficacy or safety of infigratinib.
  3. Current evidence of clinically significant corneal or retinal disorder/keratopathy confirmed by ophthalmic examination.
  4. Concurrent circumstance, disease or condition that, in the view of the investigator and/or sponsor, would interfere with study participation or safety evaluations and/or would require treatment with a prohibited medication, and/or would place the subject at high risk for poor treatment compliance or for not completing the study.
  5. History and/or current evidence of extensive ectopic tissue calcification.

  6. History of malignancy.

     Prior/Concomitant Therapy

  7. Having received or planning to receive treatment with any other investigational or approved product for the treatment of ACH or short stature.
  8. Regular long-term treatment (≥3 weeks) with supraphysiologic doses of glucocorticoid therapy (ie, >15 mg/m2/day of hydrocortisone or equivalence) or treatment with glucocorticoids at anti-inflammatory doses for over 3 weeks within 6 months of the screening visit (low-dose ongoing inhaled steroid for asthma is acceptable).
  9. Previous limb-lengthening surgery at any time or planned/expected to have limb-lengthening surgery or guided growth surgery during the study period. Guided growth surgery with plates removed at least 12 months prior to screening is allowed.
  10. Currently receiving treatment with agents that are known strong inducers or inhibitors of CYP3A4 or prolonged treatment (>1 week) with medications that alter the pH of the gastrointestinal tract or antiepileptic drugs that are CYP3A4 and/or P-gp inducers, including carbamazepine, phenytoin, phenobarbital, and primidone.

  11. Current evidence of endocrine alterations of calcium/phosphorus homeostasis.

      Diagnostic assessments

  12. Subjects who have significant abnormality in screening laboratory results.

      Other Exclusions

  13. Having had a fracture of the long bones (ie, extremities) or spine within 12 months prior to screening.
  14. Pregnant or breastfeeding at the screening visit or planning to become pregnant (self or partner) at any time during the study.
  15. Allergy or hypersensitivity to any components of the study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Infigratinib 0.25 mg/kg/day; Infigratinib at 2, 3.5, 5, 7, 10 mg	Drug: Infigratinib 0.25 mg/kg/day; Daily doses of oral Infigratinib (sprinkle capsules) at 2, 3.5, 5, 7, 10 mg
Placebo Comparator: Placebo 0.25 mg/kg/day; Placebo Comparator at 2, 3.5, 5, 7, 10 mg	Drug: Placebo Comparator 0.25 mg/kg/day; Daily doses of oral Placebo Comparator (sprinkle capsules) at 2, 3.5, 5, 7, 10 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline (BL) in annualized height velocity (cm/year)	Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from BL in height Z-score (in relation to ACH tables)		Week 52
Change from BL in upper to lower body segment ratio		Week 52
Change from BL in height Z-score (in relation to non-ACH tables)		Week 52
Annualized height velocity (cm/year)		Week 52
Absolute and change from baseline in upper arm to forearm length ratio (cm)		Week 52
Absolute and change from baseline in upper leg to lower leg length ratio (cm)		Week 52
Absolute and change from baseline in arm span (cm) to standing height ratio		Week 52
Absolute and change from baseline in head circumference (cm) to standing height ratio		Week 52
Absolute value and change in body mass index		Week 52
Incidence of adverse events		Week 52
Change from BL in annualized height velocity (cm/year) in children 5 years old and older, compared to placebo		Week 52
Change from BL in the Physical Functioning dimension of the Pediatric Quality of Life Generic Core Scale Short Form	Scale scores 0-100. Higher score=better Health-Related Quality of Life	Week 52
Change in psychomotor function assessed by age-appropriate computerized tests (Detection Test), compared to placebo	Lower score=better performance. Range values=2-6	Week 52
Change from BL in attention assessed by age-appropriate computerized tests (Identification Test)	Lower score=better performance. Range values=2-6	Week 52
Change from BL in visual learning assessed by age-appropriate computerized tests (One Card Learning Test)	Higher score=better performance. Range values=0-1.6	Week 52
Change from BL in working memory assessed by age-appropriate computerized tests (One Back Test)	Lower score=better performance. Range values=2-6	Week 52
Pharmacokinetic profile of infigratinib by assessment of maximum concentration (Cmax)		Week 52
Pharmacokinetic profile of infigratinib by assessment of time-to-maximum concentration (Tmax)		Week 52
Evaluate the acceptability and palatability of infigratinib using a 5-point hedonic scale		Week 13
Change from BL in collagen X marker concentration (ug/L)		Week 52

Collaborators and Investigators

• Sponsor: QED Therapeutics, Inc.
• Investigators: Study Director: QED Therapeutics, Inc. Medical Director, Clinical Development, QED Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): April 30, 2026

Study Registration Dates

• First Submitted: November 29, 2023
• First Submitted That Met QC Criteria: December 8, 2023
• First Posted (Actual): December 11, 2023

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Growth; FGFR3; Genetic diseases; Bone disease; Dwarfism; Skeletal dysplasia; Endochondral ossification; Fibroblast growth factor receptor 3; Endochondral bone formation; Short-limb disproportionate dwarfism; Musculoskeletal diseases; Osteochondrodysplasia; Long-term treatment; Quality of life in achondroplasia; Functionality in achondroplasia; Annualized height velocity
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Musculoskeletal Diseases; Bone Diseases; Dwarfism; Bone Diseases, Developmental; Osteochondrodysplasias; Achondroplasia; Antineoplastic Agents; Infigratinib
• Other Study ID Numbers: QBGJ398-303

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No